CN101284803A - Synthetic method of N-fluorenylmethoxycarbonyl-O-tert-butyl serine - Google Patents
Synthetic method of N-fluorenylmethoxycarbonyl-O-tert-butyl serine Download PDFInfo
- Publication number
- CN101284803A CN101284803A CNA2008100434537A CN200810043453A CN101284803A CN 101284803 A CN101284803 A CN 101284803A CN A2008100434537 A CNA2008100434537 A CN A2008100434537A CN 200810043453 A CN200810043453 A CN 200810043453A CN 101284803 A CN101284803 A CN 101284803A
- Authority
- CN
- China
- Prior art keywords
- tert
- nyl
- serine
- butyl
- butyl serine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for synthesizing N-fluorenylmethoxycarbonyl-O-tert-butyl serine which mainly solves the technical problems that: the prior synthetic method has more steps and long period, uses flammable and explosive raw materials with bigger toxicity, and has serious three-waste pollution and high cost. The invention adopts the technical proposal that: the method for synthesizing N-fluorenylmethoxycarbonyl-O-tert-butyl serine comprises the following steps that: a. serine is aerated with HCl gas in anhydrous methanol solvent to react for 10 to 14 hours, and then is distilled to obtain serine methyl ester hydrochloride; b. the serine methyl ester hydrochloride is directly aerated with isobutene, with dioxane or methylene dichloride as solvent under the catalyzing of paratoluenesulfonic acid, to react to obtain O-tert-butyl serine methyl ester; c. the O-tert-butyl serine methyl ester is directly saponified to obtain O--tert-butyl serine; d. and the O-tert-butyl serine is reacted with Fmoc-Cl or Fmoc-osu for 2 to 5 hours to obtain the N-fluorenylmethoxycarbonyl-O-tert-butyl serine. The obtained product of the invention is the important raw material for synthesizing polypeptide.
Description
Technical field:
The present invention relates to a kind of synthetic method of N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine, the N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine of acquisition is the raw material of a very important synthetic polypeptide.
Background technology:
The synthetic route of at present synthetic N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine is as follows:
A. Serine feeds HCl gas in the anhydrous methanol solvent, reacts after 12 hours to obtain serine methyl ester hydrochloride after the distillation;
B. serine methyl ester hydrochloride and carbobenzoxy-(Cbz) acyl chlorides room temperature reaction obtain N-carbobenzoxy-(Cbz)-serine methylester;
C.N-carbobenzoxy-(Cbz)-serine methylester feeds isobutene gas under vitriolic catalysis,, react and obtained N-carbobenzoxy-(Cbz)-O-tert-butyl serine methyl esters in 96 hours as solvent with methylene dichloride or dioxane;
D.N-carbobenzoxy-(Cbz)-O-tert-butyl serine methyl esters saponification reaction in methyl alcohol or acetone solvent obtained N-carbobenzoxy-(Cbz)-O-tert-butyl serine in 10 hours;
E.N-carbobenzoxy-(Cbz)-O-tert-butyl serine is made catalyzer with palladium carbon, and logical hydrogen reaction obtains the O-tert-butyl serine;
The f.O-tert-butyl serine obtained the N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine in 3 hours with Fmoc-Cl or Fmoc-osu reaction.
Its process flow steps is:
H-Ser-OH to H-Ser-OME.HCl is many to Z-Ser-OME to Z-Ser (tBu)-OME to Z-Ser (tBu)-OH to H-Ser (tBu)-OH to Fmoc-Ser (tBu)-this process flow steps of oh, cycle is long, and this route is used raw material inflammable and explosive and that toxicity is bigger, three-waste pollution is serious, the cost height, comprehensive benefit is poor.Therefore it is extremely important to develop the little technology of low-cost and easy-to operational danger.
Summary of the invention:
Purpose of the present invention:
The synthetic method of N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine is provided, and it is many mainly to solve the step that former synthetic method exists, and the cycle is long, and this route uses raw material inflammable and explosive and that toxicity is bigger, and three-waste pollution is serious, the technical problem that cost is high.
Technical scheme of the present invention is: a kind of synthetic method of N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine may further comprise the steps:
A. Serine feeds HCl gas in the anhydrous methanol solvent, reacts after 10-14 hour to obtain serine methyl ester hydrochloride after the distillation;
B. serine methyl ester hydrochloride is that solvent directly feeds under Catalyzed by p-Toluenesulfonic Acid and obtained O-tert-butyl serine methyl esters in isobutene reaction 48-96 hour at dioxane or methylene dichloride;
Obtained the O-tert-butyl serine in the direct saponification 1-5 of c.O-tert-butyl serine methyl esters hour;
The d.O-tert-butyl serine obtained the N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine in 2-5 hour with Fmoc-Cl or Fmoc-osu reaction.
Process flow steps of the present invention is:
H-Ser-OH to H-Ser-OME.HCl is to H-Ser (tBu)-OMe.TOS to H-Ser (tBu)-OH to Fmoc-Ser (tBu)-OH
Among the step b: serine methyl ester hydrochloride, tosic acid and solvent dioxane or methylene dichloride weight ratio are by 1: (1-8): mixed (15-20), controlled temperature is at-20 ℃ to-5 ℃, in mixed system, add iso-butylene, closed system afterwards, be warmed up to 5-10 ℃ of reaction 48-96 hour, distillation was sloughed solvent and is obtained O-tert-butyl serine methyl esters tosilate after reaction finished.
The described saponification reaction of step c: O-tert-butyl serine methyl esters tosilate directly and solvent methanol or acetone weight ratio be 1: (8-20) mixing, add the proper amount of sodium hydroxide aqueous solution down at temperature 5-35 ℃, saponification reaction 1-5 obtained the O-tert-butyl serine in individual hour.
In the steps d: add an amount of Fmoc-Cl or Fmoc-osu (being dissolved in the acetonitrile of 5 times of weight) in the O-tert-butyl serine solution system that obtains, room temperature reaction 2-5 hour, acidification obtained the N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine afterwards.
The invention has the beneficial effects as follows: the present invention is the beginning raw material by serine methyl ester hydrochloride, and one kettle way synthesizes the N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine, does not need to handle out intermediate, step is simple, it is convenient to handle, and has saved the raw material solvent of intermediate treatment greatly, reduces cost.Reduced middlely, and saved and need this inflammable and explosive raw material of hydrogen in the hydrogenation, shortened the production cycle with this toxicity of Carbobenzoxy Chloride and the bigger raw material of damage ratio, simple to operate.
The abbreviation of using among the present invention is expressed as follows:
Fmoc: fluorenylmethyloxycarbonyl
Fmoc-osu: fluorenes methoxy carbonyl acyl succinimide
Fmoc-Cl: fluorenes methoxy dicarbonyl chloride
TBu: the tertiary butyl
Ser: Serine
Me: methyl
Z: carbobenzoxy-(Cbz)
O: oxygen
N: nitrogen
TOS: tosic acid base
Z-Ser-OMe:N-carbobenzoxy-(Cbz)-serine methylester
Z-Ser (tBu)-OMe:N-carbobenzoxy-(Cbz)-O-tert-butyl serine methyl esters
H-Ser-OME.HCl: serine methyl ester hydrochloride
H-Ser (tBu)-OMe.TOS:O-tert-butyl serine methyl esters tosilate
Z-Ser (tBu)-OH:N-carbobenzoxy-(Cbz)-O-tert-butyl serine
H-Ser (tBu)-OH:O-tert-butyl serine
Fmoc-Ser (tBu)-OH:N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine
Embodiment:
The present invention includes but be not limited to following example:
Embodiment 1
The preparation of serine methyl ester hydrochloride: 10 kilograms of Serines are dropped in 100 kilograms of anhydrous methanols, feed 15 kilograms of HCl under the room temperature, reacted 10 hours, distillation is afterwards desolvated and is obtained 13.4 kilograms of serine methyl ester hydrochlorides.The preparation of O-tert-butyl serine methyl esters tosilate: upward go on foot the serine methyl ester hydrochloride that obtains and join in 200 kilograms of dioxane for 13.4 kilograms, adding 80 kilograms of tosic acid, temperature-5 ℃ adding iso-butylene, 10 ℃ of reactions of temperature 48 hours are sloughed solvent and are obtained O-tert-butyl serine methyl esters tosilate.
The preparation of O-tert-butyl serine: O-tert-butyl serine methyl esters tosilate is put in 320 kilograms of methyl alcohol, added 25 kilograms of aqueous sodium hydroxide solutions, 5 ℃ of temperature were reacted 1 hour, obtained the methanol aqueous solution of O-tert-butyl serine.
The preparation of N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine: Fmoc-osu22.5 kilogram (being dissolved in 112 kilograms of acetonitriles) is added in the previous step system, room temperature reaction 2 hours, hcl acidifying afterwards, the dichloromethane extraction layering, neutral siccative drying is sloughed solvent and is obtained 21.9 kilograms of N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serines, the total yield is 60%.HPLC=99.6%, fusing point 129.9-130.3 ℃, optically-active 24.1 (C=1, vinyl acetic monomer).
Embodiment 2
The preparation of serine methyl ester hydrochloride: Serine drops in 800 kilograms of anhydrous methanols for 80 kilograms, feeds the HCl120 kilogram under the room temperature, reacts 12 hours, and distillation is afterwards desolvated and obtained 106 kilograms of serine methyl ester hydrochlorides.The preparation of O-tert-butyl serine methyl esters tosilate: upward in 1800 kilograms of methylene dichloride of 106 kilograms of serine methyl ester hydrochlorides inputs that the step obtains, add 632 kilograms of tosic acid, temperature-20 ℃ adding iso-butylene, 10 ℃ of reactions of temperature afterwards 72 hours are sloughed methylene dichloride and are obtained O-tert-butyl serine methyl esters tosilate.The preparation of O-tert-butyl serine: O-tert-butyl serine methyl esters tosilate is put in 2000 kilograms of acetone, added 200 kilograms of aqueous sodium hydroxide solutions, 5 ℃ of temperature were reacted 3 hours, obtained the aqueous acetone solution of O-tert-butyl serine.
The preparation of N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine: Fmoc-osu192 kilogram (being dissolved in 960 kilograms of acetonitriles) is added in the previous step system, room temperature reaction 3 hours, hcl acidifying afterwards, the dichloromethane extraction layering, neutral siccative drying, slough solvent, obtain 179.6 kilograms of N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serines.The total yield is 61.5%.HPLC=99.31%, fusing point 128.8-131.1 ℃, and optically-active 23.9 (C=1, vinyl acetic monomer).
Embodiment 3
The preparation of serine methyl ester hydrochloride: 100 kilograms of Serines are dropped in 1000 kilograms of anhydrous methanols, feed 150 kilograms of HCl under the room temperature, reacted 14 hours, distillation is afterwards desolvated and is obtained 135 kilograms of serine methyl ester hydrochlorides.The preparation of O-tert-butyl serine methyl esters tosilate: upward go on foot the serine methyl ester hydrochloride that obtains and join in 2000 kilograms of dioxane for 135 kilograms, adding 800 kilograms of tosic acid, temperature-5 ℃ adding iso-butylene, 10 ℃ of reactions of temperature 96 hours are sloughed solvent and are obtained O-tert-butyl serine methyl esters tosilate.
The preparation of O-tert-butyl serine: O-tert-butyl serine methyl esters tosilate is put in 3200 kilograms of methyl alcohol, added 250 kilograms of aqueous sodium hydroxide solutions, 5 ℃ of temperature were reacted 5 hours, obtained the methanol aqueous solution of O-tert-butyl serine.
The preparation of N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine: Fmoc-osu226 kilogram (being dissolved in 1120 kilograms of acetonitriles) is added in the previous step system, room temperature reaction 5 hours, hcl acidifying afterwards, the dichloromethane extraction layering, neutral siccative drying is sloughed solvent and is obtained 210 kilograms of N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serines, the total yield is 57.5%.HPLC=99.53%, fusing point 130.2-133.3 ℃, optically-active 24.8 (C=1, vinyl acetic monomer).
Amino acid among the present invention is the Serine of L type, if be changed to D type or D, L type Serine, can make the N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine of respective configuration, step in the production, ratio of components, the working condition unanimity, the yield of products obtained therefrom, purity fusing point basically identical.
Claims (7)
1, a kind of synthetic method of N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine is characterized in that may further comprise the steps:
A. Serine feeds HCl gas in the anhydrous methanol solvent, reacts after 10-14 hour to obtain serine methyl ester hydrochloride after the distillation;
B. serine methyl ester hydrochloride is that solvent directly feeds isobutene reaction and obtained O-tert-butyl serine methyl esters in 48-96 hour under Catalyzed by p-Toluenesulfonic Acid at dioxane or methylene dichloride;
Obtained the O-tert-butyl serine in the direct saponification 1-5 of c.O-tert-butyl serine methyl esters hour;
The d.O-tert-butyl serine obtained the N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine in 2-5 hour with fluorenes methoxy dicarbonyl chloride or the reaction of fluorenes methoxy carbonyl acyl succinimide.
2, the synthetic method of a kind of N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine according to claim 1 is characterized in that among the step b: serine methyl ester hydrochloride, tosic acid and solvent dioxane or methylene dichloride weight ratio are by 1: (1-8): mixed (15-20).
3, the synthetic method of a kind of N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine according to claim 1 is characterized in that: add iso-butylene among the step b in mixed system, controlled temperature is at-20 ℃ to-5 ℃.
4, the synthetic method of a kind of N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine according to claim 1 is characterized in that: the temperature of reaction of step b is 5-10 ℃.
5, the synthetic method of a kind of N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine according to claim 1 is characterized in that: the described saponification reaction of step c is: O-tert-butyl serine methyl esters tosilate directly and solvent methanol or acetone weight ratio be 1: (8-20) mixing.
6, the synthetic method of a kind of N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine according to claim 1 is characterized in that: step c temperature of reaction is 5-35 ℃.
7, the synthetic method of a kind of N-fluorenylmethoxycarb-nyl-nyl O-tert-butyl serine according to claim 1 is characterized in that: fluorenes methoxy dicarbonyl chloride or fluorenes methoxy carbonyl acyl succinimide are dissolved in the acetonitrile of 5 times of weight in the steps d.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100434537A CN101284803B (en) | 2008-06-06 | 2008-06-06 | Synthetic method of N-fluorenylmethoxycarbonyl-O-tert-butyl serine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100434537A CN101284803B (en) | 2008-06-06 | 2008-06-06 | Synthetic method of N-fluorenylmethoxycarbonyl-O-tert-butyl serine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101284803A true CN101284803A (en) | 2008-10-15 |
| CN101284803B CN101284803B (en) | 2012-01-04 |
Family
ID=40057238
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008100434537A Active CN101284803B (en) | 2008-06-06 | 2008-06-06 | Synthetic method of N-fluorenylmethoxycarbonyl-O-tert-butyl serine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101284803B (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103232370A (en) * | 2013-05-09 | 2013-08-07 | 成都郑源生化科技有限公司 | Preparation method of fmoc chloride glutamic acid-4-tert-butyl ester |
| CN103833593A (en) * | 2014-03-21 | 2014-06-04 | 四川什邡市三高生化实业有限公司 | Method for preparing N-(9-fluorenylmethoxy carbony)-O-tertiary butyl-L-tyrosine |
| CN108358816A (en) * | 2018-02-05 | 2018-08-03 | 南京法恩化学有限公司 | A kind of synthetic method of N- fluorenylmethyloxycarbonyls ethylenediamine ethyl acrylates hydrochloride |
| CN109134314A (en) * | 2018-09-17 | 2019-01-04 | 吉尔生化（上海）有限公司 | A kind of preparation method of polypeptide raw material N- fluorenylmethoxycarb-nyl -nyl O-tert-butyl threonine |
| CN109232321A (en) * | 2018-09-25 | 2019-01-18 | 成都市科隆化学品有限公司 | A kind of Fmoc-Thr(tBu)-OH preparation method |
| CN109265370A (en) * | 2018-09-25 | 2019-01-25 | 四川什邡市三高生化实业有限公司 | A kind of preparation method of N- (9-fluorenylmethyloxycarbonyl)-O- tert-butyl-Serine |
| CN109627185A (en) * | 2018-12-03 | 2019-04-16 | 吉尔生化（上海）有限公司 | A kind of preparation method of N- fluorenylmethyloxycarbonyl-O- caprylyl-serine/threonine |
| CN110627686A (en) * | 2019-09-11 | 2019-12-31 | 上海吉奉生物科技有限公司 | Synthesis method of fluorenylmethyloxycarbonyl-O-trityl-L-threonine |
| CN116082190A (en) * | 2022-12-29 | 2023-05-09 | 常州吉恩药业有限公司 | Industrial production method of efficient Fmoc-Ser (tBu) -OH |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100491345C (en) * | 2005-03-21 | 2009-05-27 | 吉尔生化（上海）有限公司 | Process for liquid phase synthesis of N-fluorenyl-methoxy-carbonyl-N-methyl-O-tertiary butyl serine |
-
2008
- 2008-06-06 CN CN2008100434537A patent/CN101284803B/en active Active
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103232370A (en) * | 2013-05-09 | 2013-08-07 | 成都郑源生化科技有限公司 | Preparation method of fmoc chloride glutamic acid-4-tert-butyl ester |
| CN103833593A (en) * | 2014-03-21 | 2014-06-04 | 四川什邡市三高生化实业有限公司 | Method for preparing N-(9-fluorenylmethoxy carbony)-O-tertiary butyl-L-tyrosine |
| CN103833593B (en) * | 2014-03-21 | 2016-08-17 | 四川什邡市三高生化实业有限公司 | A kind of preparation method of N-(the 9-fluorenylmethyloxycarbonyl)-O-tert-butyl group-TYR |
| CN108358816A (en) * | 2018-02-05 | 2018-08-03 | 南京法恩化学有限公司 | A kind of synthetic method of N- fluorenylmethyloxycarbonyls ethylenediamine ethyl acrylates hydrochloride |
| CN109134314A (en) * | 2018-09-17 | 2019-01-04 | 吉尔生化（上海）有限公司 | A kind of preparation method of polypeptide raw material N- fluorenylmethoxycarb-nyl -nyl O-tert-butyl threonine |
| CN109232321A (en) * | 2018-09-25 | 2019-01-18 | 成都市科隆化学品有限公司 | A kind of Fmoc-Thr(tBu)-OH preparation method |
| CN109265370A (en) * | 2018-09-25 | 2019-01-25 | 四川什邡市三高生化实业有限公司 | A kind of preparation method of N- (9-fluorenylmethyloxycarbonyl)-O- tert-butyl-Serine |
| CN113135842A (en) * | 2018-09-25 | 2021-07-20 | 四川什邡市三高生化实业有限公司 | Preparation method of O-tert-butyl-L-serine methyl ester and O-tert-butyl-L-serine aqueous solution |
| CN109627185A (en) * | 2018-12-03 | 2019-04-16 | 吉尔生化（上海）有限公司 | A kind of preparation method of N- fluorenylmethyloxycarbonyl-O- caprylyl-serine/threonine |
| CN110627686A (en) * | 2019-09-11 | 2019-12-31 | 上海吉奉生物科技有限公司 | Synthesis method of fluorenylmethyloxycarbonyl-O-trityl-L-threonine |
| CN116082190A (en) * | 2022-12-29 | 2023-05-09 | 常州吉恩药业有限公司 | Industrial production method of efficient Fmoc-Ser (tBu) -OH |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101284803B (en) | 2012-01-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101284803B (en) | Synthetic method of N-fluorenylmethoxycarbonyl-O-tert-butyl serine | |
| CN103012525B (en) | Method for synthesizing emamectin benzoate | |
| RU2015129643A (en) | THE UNITED METHOD FOR PRODUCING METHYL ACETATE AND METHANOL FROM SYNTHESIS GAS AND DIMETHYL ETHER | |
| CN109534975B (en) | Catalytic synthesis method of 2-hydroxybenzophenone compound | |
| CN105237342B (en) | A kind of method that catalytic hydrogenation carboxylate reduction prepares alcohol | |
| CN100491345C (en) | Process for liquid phase synthesis of N-fluorenyl-methoxy-carbonyl-N-methyl-O-tertiary butyl serine | |
| US7799756B2 (en) | Processes for stereoselective synthesis of trans ISATX247 | |
| Oh et al. | Cycloreductions via alkylpalladium intermediates: An important mechanistic clue for palladium-catalyzed enediyne cyclizations | |
| US9376365B2 (en) | Hydrocarbonylation or methoxycarbonylation of 1,3-diene derivatives with palladium complex | |
| CN113896656B (en) | Preparation method of [2- [2- (Fmoc-amino) ethoxy ] acetic acid | |
| CN109836368B (en) | Preparation method of high-purity liraglutide side chain | |
| CN110452198B (en) | Preparation method of feloxicib | |
| KR20190054646A (en) | Process for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol | |
| CN113968834A (en) | Preparation method of 5-hydroxymethyl furoic acid | |
| CN106518865A (en) | Method for preparing 1-alkenyl indolizine derivative | |
| KR20170047802A (en) | Preparation method of dimethylterephthalate | |
| CA2647586A1 (en) | Process for producing 3-[4-(1,1-dimethyl-propyl)-phenyl]-2-methyl-propionaldehyde and cis-4-{3-[4-(1,1-dimethyl-propyl)-phenyl]-2-methyl-propyl}-2,6-dimethyl-morpholine (amorolfine) | |
| US6911562B2 (en) | Process for the preparation of a cosmetic active | |
| Kim et al. | Stereodivergent access to rocaglaol enabled by dual catalytic asymmetric allylation | |
| CN111433181A (en) | Synthesis of bicyclo [2.2.2] octane derivatives | |
| CN115417781B (en) | Method for preparing chlorantraniliprole intermediate K amine | |
| CN107445850B (en) | Preparation method of 12-aminododecanoic acid | |
| CN110078588B (en) | Preparation method of 1, 3-propylene glycol | |
| US10913702B2 (en) | Method for cycloaddition of dimethyl muconate | |
| CN111018830B (en) | Polysubstituted conjugated diene compound and synthesis method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20180425 Address after: 210047 room 329-338 and 340, Fang Shui Road, Nanjing Chemical Industrial Park, Nanjing, Jiangsu, China, 158 Patentee after: NANJING PEPTIDE BIOTECHNOLOGY CO., LTD. Address before: No. 519 purple moon Road, Minhang District, Shanghai City, Shanghai Patentee before: Glbetter Biochemical (Shanghai) Co., Ltd. |
|
| TR01 | Transfer of patent right |